The goal of the proposed research is to better understand the physiological consequences of stress or handling as these are reflected in alterations of different parameters of antibody and cell-I mediated immune responses to levels of antigenic stimulation that are more characteristic of the stimulation that occurs under natural conditions. To this end, we have proposed descriptive parametric studies to examine the development of secondary (memory) immune responses generated following low dose antigen priming in footshock stressed, handled, and control mice. We will also determine whether there are differential effects of stress on primary and secondary antibody responses in normal versus immunologically compromised (i.e., immunosuppressed) mice. Further studies, predicated on these data, will determine whether the animal's ability to predict or control the stressor alters its immunomodulatory effects and whether stress-induced changes in immunity can be conditioned. The effects of handling and footshock stress (and the degree to which the animal is capable of coping with stress) on the metastatic spread of the Line I tumor will also be studied in relation to the immunologic changes induced by these forms of stimulation. Using both in vitro and in vivo protocols, several possible mechanisms that might underlie the immunomodulatory effects of handling and footshock that have already been observed and that will be uncovered in the proposed studies will also be explored. Data from our proposed studies may be clinically relevant in situations where patients are immunosuppressive by human immunodeficiency disease (HIV) or receive immunosuppressive drugs as part of a chemotherapeutic protocol or in association with organ transplantation. These basic studies will also meet the defined need to characterize the range and parameters of immune function that are subject to the influence of environmental (e.g ., "stress") conditions and will enable a more focused approach to the neuroendocrine and immunologic mechanisms underlying the effects of stress on immunity.